不同程度内质网应激对巨噬细胞自噬的影响

目的：采用ox-LDL诱导巨噬细胞泡沫化模型,通过不同剂量衣霉素诱导巨噬细胞不同程度内质网应激,观察对其自噬的影响。方法：不同剂量衣霉素作用于小鼠巨噬细胞系RAW264．7,通过TUNEL染色检测其凋亡率,Westernblot检测内质网应激蛋白GRP78,以及自噬标志蛋白P62的表达水平。结果：与ox-LDL组和大剂量衣霉素组相比,小剂量衣霉素组可以显著减少巨噬细胞的凋亡（P〈0．01）;与ox-LDL组相比,小剂量衣霉素组上调内质网应激蛋白GRP78表达的同时,自噬标志蛋白P62适度下降（P〈0．01）;大剂量衣霉素组更为显著地上调了内质网应激蛋白GRP78表达,但同时自噬标志蛋白P62也显著增加（P〈0．01）。结论：小剂量衣霉素引起一定程度的内质网应激,可以激活适度的自噬,从而减少巨噬细胞的凋亡,可能有助于降低动脉粥样硬化的程度。     

不同程度内质网应激对巨噬细胞自噬的影响*

摘要目的：采用ox-LDL诱导巨噬细胞泡沫化模型,通过不同剂量衣霉素诱导巨噬细胞不同程度内质网应激,观察对其自噬的影 响。方法：不同剂量衣霉素作用于小鼠巨噬细胞系RAW264.7,通过TUNEL染色检测其凋亡率,Western blot检测内质网应激蛋白 GRP78,以及自噬标志蛋白P62 的表达水平。结果：与ox-LDL组和大剂量衣霉素组相比,小剂量衣霉素组可以显著减少巨噬细胞 的凋亡（P<0.01）;与ox-LDL 组相比,小剂量衣霉素组上调内质网应激蛋白GRP78表达的同时,自噬标志蛋白P62 适度下降（P< 0.01）;大剂量衣霉素组更为显著地上调了内质网应激蛋白GRP78 表达,但同时自噬标志蛋白P62 也显著增加（P<0.01）。结论：小 剂量衣霉素引起一定程度的内质网应激,可以激活适度的自噬,从而减少巨噬细胞的凋亡,可能有助于降低动脉粥样硬化的程 度。     

葛根素延缓动脉粥样硬化进展的机制研究

目的:明确葛根素(Pur)对小鼠动脉粥样硬化斑块稳定性的治疗作用及其潜在机制。方法:用高脂饮食喂养成年小鼠诱导动脉粥样硬化模型,将小鼠分为Con组,ApoE~(-/-)组,ApoE~(-/-)+Pur组。采用HE染色分别检测各组小鼠中动脉粥样硬化斑块面积,免疫荧光染色检测斑块中MMP2的阳性区域面积。用50μg/mL ox-LDL干预巨噬细胞诱导动脉粥样硬化细胞模型,并用Ad-sh-Sirt3干扰Sirt3表达,将细胞分为Con组、ox-LDL组、ox-LDL+Pur组、ox-LDL+Pur+Ad-sh-Sirt3组。Western-blot检测Sirt3表达含量,TUNEL法检测巨噬细胞凋亡。结果:动物水平,与Con组相比,ApoE~(-/-)组小鼠出现了显著的动脉粥样硬化斑块,ApoE~(-/-)组小鼠MMP2阳性区域面积显著高于Con组(P0.05);Pur处理后,ApoE~(-/-)+Pur组动脉粥样硬化斑块面积明显低于ApoE~(-/-)组(P0.05),MMP2的阳性区域面积显著低于ApoE~(-/-)组(P0.05)。细胞水平,Western结果显示,与对照组相比,ox-LDL组Sirt3表达量显著降低(P0.05),ox-LDL+Pur组Sirt3表达水平显著高于ox-LDL组(P0.05)。相比于Con组,ox-LDL组巨噬细胞凋亡水平显著升高(P0.05);给予Pur处理后,相比于单纯ox-LDL组,ox-LDL+Pur组巨噬细胞的凋亡水平显著降低(P0.05)。Ad-sh-Sirt3处理消除了葛根素对于巨噬细胞凋亡的抑制作用(P0.05)。结论:外源性Pur可能通过激活Sirt3表达,进一步降低巨噬细胞凋亡水平,减少巨噬细胞的浸润,增加动脉粥样硬化斑块稳定性。     

巨噬细胞的自噬和极化抑制其泡沫化进程

目的:巨噬细胞是动脉粥样硬化斑块中最丰富的免疫细胞,巨噬细胞泡沫化加速动脉粥样硬化,本研究探讨巨噬细胞自噬与极化对泡沫化的影响。方法:分离培养小鼠腹腔巨噬细胞,免疫荧光检测巨噬细胞的标记物F4/80。不同浓度雷帕霉素处理巨噬细胞,western blot检测自噬标记物LC3II,经典激活的巨噬细胞(Classically activated macrophages, M1)标记物白细胞介素6(interleukin 6, IL-6)和替代激活的巨噬细胞(Alternatively activated macrophages, M2)标记物转化生长因子β(transform growth factor,TGF-β)的表达。用ox-LDL诱导巨噬细胞泡沫化,油红O染色鉴定泡沫细胞形成及巨噬细胞泡沫化情况。结果:免疫荧光结果显示,小鼠腹腔巨噬细胞F4/80阳性率达87.6%;雷帕霉素处理巨噬细胞24 h,western blot结果显示LC3II表达增加,M1标记物IL-6表达增加,而M2标记物TGF-β表达减少,对其条带进行统计分析结果显示都具有显著性差异(P0.05);油红O染色结果显示雷帕霉素明显减少巨噬细胞泡沫化形成。结论:雷帕霉素能诱导巨噬细胞自噬,促进其向M1型极化,从而抑制巨噬细胞泡沫化。     

CHOP双重调控衣霉素诱导的DU-145细胞凋亡及自噬的研究

目的研究内质网应激分子CHOP调控细胞凋亡与自噬的作用和机制。 方法利用衣霉素诱导DU-145细胞产生内质网应激,Western Blot法检测内质网应激相关分子Grp78、Grp94、p-eIF2α和CHOP及自噬蛋白LC3Ⅱ、Atg5和Beclin1的表达;用流式细胞术检测细胞凋亡水平;沉默CHOP基因,用Western Blot法检测凋亡蛋白PARP、Caspase3的表达,流式细胞术检测细胞凋亡;并利用免疫荧光检测自噬标志性蛋白LC3B的表达。 结果衣霉素诱导DU-145细胞内质网应激能诱导一定程度的细胞凋亡,衣霉素处理8、12、24?h的细胞凋亡率分别为3.27﹪±1.02﹪,8.97﹪±0.71﹪和11.67﹪±1.41﹪,处理12?h及24?h的细胞凋亡率与对照组相比差异具有统计学意义（P < 0.01）。同时也能通过抑制PI3K/AKt/mTOR信号通路激活DU-145细胞自噬。CHOP基因沉默抑制细胞凋亡,shCtrl组细胞凋亡率为32.17﹪±3.93﹪,shCHOP-1组细胞凋亡率为23.53﹪±3.41﹪,两组相比差异具有统计学意义（P < 0.05）。且CHOP基因沉默能促进细胞自噬分子LC3B的表达。 结论衣霉素诱导DU-145细胞内质网应激状态下,CHOP在细胞凋亡与自噬之间发挥双重调控作用。     

过表达apoA-I可缓解BEL-7402细胞中衣霉素诱导的内质网应激

内质网应激（endoplasmic reticulum stress,ER stress）对非酒精性脂肪性肝病（non alcoholic fatty liver disease,NAFLD）的发生发展具有十分重要的作用。本实验室前期结果证实,载脂蛋白A1（apolipoprotein A-I,apoA-I）可以通过减少肝细胞脂质堆积来减轻蛋氨酸胆碱缺乏饲料造成的非酒精性肝炎(non-alcoholic steatohepatitis,NASH),但相关机制仍不十分清楚。为探索apoA I对内质网应激的影响,本研究采用衣霉素处理人肝癌BEL-7402细胞。Western印迹结果证实,衣霉素确实可以诱导BEL-7402细胞内质网应激,并具有时间和剂量依赖性。通过将apoA-I表达载体及其对照载体转染到BEL-7402细胞,再加入衣霉素处理,结果显示,与对照组相比,过表达apoA-I的细胞内质网应激标志分子表达明显减轻,同时与脂质合成相关的固醇调节元件结合蛋白1、脂肪酸合成酶和乙酰辅酶A羧化酶1蛋白质水平明显降低。脂质检测结果表明,细胞内甘油三酯和游离胆固醇水平也明显降低（P<0.05）。上述结果表明,apoA-I能够减轻衣霉素引起的内质网应激,可能机制是通过调控固醇调节元件结合蛋白1减少肝细胞的脂质堆积。     

内质网应激预处理条件下大鼠肝脏缺血再灌注损伤模型的建立

目的:通过建立了内质网应激预处理条件下的大鼠肝脏缺血再灌注损伤模型,探讨内质网应激预处理在体内的应用.方法:以衣霉素为内质网应激诱导剂,采用大鼠肝脏70%缺血再灌注损伤模型.按照不同给药剂量分为50μ g/kg组、100μ g,kg组、200μ g/kg组、对照组,观察不同给药剂量条件下,血清转氨酶水平的变化.结果:给药100μ g/kg体重、诱导5天条件下大鼠术后转氨酶水平显著低于对照组.其它组与对照组无统计学差异.肝组织病理切片证实该预处理条件对肝脏缺血再灌注损伤有显著保护作用.结论:在特定的给药剂量条件下,衣霉素诱导的内质网应激预处理对大鼠肝脏缺血再灌注损伤有显著的保护作用.     

Aliskiren单用及联用氟伐他汀对动脉粥样硬化斑块稳定性的影响

目的:观察和比较肾素抑制剂aliskiren单用或与氟伐他汀(fluvastatin)联用对动脉粥样硬化斑块稳定性的影响。方法:选择4周龄雄性ApoE-/-小鼠通过喂以高脂饮食8周建立动脉粥样硬化模型,将其随机分为5组:模型对照组、aliskiren组、肼屈嗪组、氟伐他汀组、aliskiren与氟伐他汀联合用药组,所有组别均治疗12周。取主动脉根部组织评估斑块面积(HE染色)、斑块内新生血管数量(CD31染色)及斑块稳定性指标(胶原蛋白染色、弹力纤维染色、Mac-3染色、MCP-1染色)。结果:与模型对照组比较,aliskiren单用显著降低动脉粥样硬化斑块面积,减少斑块内新生血管数量以及巨噬细胞浸润、炎症因子表达,增加斑块内弹力纤维及胶原蛋白含量(P0.05或P0.01)。与aliskiren单用组比较,aliskiren与氟伐他汀联用进一步降低斑块面积,改善斑块的稳定性(P0.05或P0.01)。与aliskiren组比较,肼屈嗪组降压幅度相似(P0.05)。与模型对照组比较,肼屈嗪没有明显抑制斑块进展以及改善斑块的稳定性(P0.05)。结论:Aliskiren能够抑制动脉粥样硬化斑块的进展,减少斑块内新生血管形成,改善斑块的稳定性,而其与氟伐他汀联用的治疗效果更佳。     

高脂饮食对小鼠附睾内质网应激的影响及褪黑素的干预作用

目的探讨内质网应激在高脂饮食引起的ApoE基因敲除小鼠附睾损伤中的作用及褪黑素（MT）的干预机制。方法将12只ApoE基因敲除的C57BL／6J雄性小鼠随机分为高脂饮食组及MT处理组。高脂饮食组为ApoE基因敲除小鼠,给予高脂饮食;MT处理组给予高脂饲养外,并MT灌胃。以6只野生型C57BL／6J雄性小鼠作为对照组,给予普通饮食。饲养12w后,取附睾组织制片,HE染色观察附睾的病理学形态,免疫组化检测GRP78和CHOP的表达。结果HE染色显示,高脂饮食组小鼠,附睾上皮细胞形态结构不清,细胞萎缩。对照组和褪黑素处理组小鼠附睾上皮细胞形态结构完整,细胞排列整齐。免疫组化显示高脂饮食组小鼠附睾中GRP78、CHOP表达增强（P〈0．01）。MT处理组和高脂饮食组相比,附睾中GRP78、CHOP表达下调（P〈0．01）。结论内质网应激参与高脂饮食导致的附睾损伤;MT可能通过抑制附睾内质网应激,减轻高脂饮食对小鼠附睾的损伤。     

Reduction of TMAO level enhances the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red, Perl’s staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells with no obvious effect on the M1 polarization. In conclusion, the present study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.     

糖尿病和非糖尿病动脉粥样硬化兔模型的建立

目的建立兔动脉粥样硬化和糖尿病动脉粥样硬化模型并比较其动脉粥样硬化病变的特点。方法四氧嘧啶静脉推注诱发糖尿病后,行腹主动脉球囊损伤术拉伤内皮并饲高脂饲料建立糖尿病动脉粥样硬化兔模型,非糖尿病动脉粥样硬化兔模型静脉推注生理盐水,余处理相同。喂养10周做腹主动脉造影和腹主动脉内超声后处死,取腹主动脉横切片做HE染色和免疫组化,比较两组兔主动脉内膜/中膜比值及巨噬细胞、平滑肌细胞含量,以评价动脉粥样硬化病变的程度和性质。结果所有兔胸主动脉粥样硬化病变明显轻于腹主动脉;糖尿病动脉粥样硬化兔腹主动脉壁特别是近血管腔处巨噬细胞浸润明显多于动脉粥样硬化兔,而平滑肌细胞含量显著减少。结论糖尿病动脉粥样硬化兔的腹主动脉粥样硬化病变内有更加活跃的炎症细胞浸润,提示病变性质更加不稳定。     

急性脑梗死患者血清RBP、NLR、PTX3水平与颈动脉粥样硬化斑块稳定性的关系研究

目的:探讨急性脑梗死(ACI)患者血清视黄醇结合蛋白(RBP)、中性粒细胞与淋巴细胞比值(NLR)、内正五聚蛋白3(PTX3)水平与颈动脉粥样硬化斑块稳定性的关系。方法:收集我院2017年1月～2019年1月收治的300例ACI患者,根据颈动脉粥样硬化斑块超声结果分为稳定斑块组(n=173)和不稳定斑块组(n=127),另选同期在我院体检中心进行健康体检的志愿者100例为对照组。对ACI患者和对照组进行RBP、NLR、PTX3、血脂指标的检测,并进行组间统计学对比。采用Pearson检验对ACI患者的RBP、NLR、PTX3与血脂指标的相关性进行分析。结果:三组受试者性别、年龄、体质指数(BMI)、吸烟史、饮酒史等基础资料对比无显著性差异(P0.05)。稳定斑块组、不稳定斑块组患者的RBP、NLR、PTX3水平均高于对照组,且不稳定斑块组上述指标水平高于稳定斑块组(P0.05)。稳定斑块组、不稳定斑块组患者的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、纤维蛋白原(FIB)水平均高于对照组,且不稳定斑块组上述指标水平高于稳定斑块组(P0.05)。经Pearson检验分析,ACI患者的RBP、NLR、PTX3水平与TC、TG、LDL-C、FIB均呈正相关性(P0.05)。结论:在ACI患者中RBP、NLR、PTX3水平较高,并与患者的颈动脉粥样硬化斑块的稳定性有紧密的关联性。初步推测RBP、NLR、PTX3可能参与颈动脉粥样硬化斑块的形成,进而影响ACI疾病的发生发展过程。     

Prostaglandin E1 dose-dependently promotes stability of atherosclerotic plaque in a rabbit model

This study evaluated the effect of prostaglandin E1 (PGE1) on the stability of atherosclerotic plaque. A vulnerable plaque model was established in rabbits, using balloon injury combined with a high-cholesterol diet. The rabbits were distributed into a control group, a low-dose PGE1 treatment group, a moderate-dose PGE1 treatment group, a high-dose PGE1 treatment group, and a simvastatin treatment group, with treatments lasting for 4?weeks. At week 13 (at the end of the experiments), atherosclerotic plaque was triggered by injection of Russell's viper venom (Chinese) and histamine. Serological, pathological, immunohistochemical, and gene-expression studies were subsequently performed. PGE1 treatment did not alter serum lipid levels; however, PGE1 dose-dependently increased the thickness of the fibrous caps, and decreased the plaque vulnerability index. The plaque contents of macrophage- and the mRNA levels of monocyte-chemotactic protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9 were markedly reduced in all of the PGE1 treatment groups, with the high-dose of PGE1 being more effective than the simvastatin treatment. These findings suggest that PGE1 dose-dependently enhances the stability of atherosclerotic plaque. The high-dose of PGE1 presented more protection in terms of inhibiting macrophage accumulation and inflammatory expression in plaque. Our findings suggest a novel drug for the treatment of atherosclerosis.     

液氮冻伤术建立动脉粥样硬化破裂斑块及血栓模型

目的创建一种操作简单、经济实用的动脉粥样硬化（AS）破裂斑块及血栓动物模型。方法21只雄性纯种新西兰白兔随机分为两组：液氮冻伤＋高脂喂养组（A组=11只）和高脂喂养组（B组=10只）。A组实施右颈总动脉内膜液氮冻伤术结合高脂饲料喂养,B组单纯给予高脂饲料喂养。8周末以液氮激发斑块破裂,激发前后分别采血检测血脂、hsC-RP、MMP-9及PAI-1水平;激发48h后处死所有动物,取出右颈总动脉作HE染色及免疫组化染色等,光镜及电镜观察破裂斑块及血栓形成情况。结果8周后兔血脂水平明显升高;激发后血浆hsC-RP、MMP-9及PAI-1均明显升高;所有A组兔子的右颈总动脉均可见AS破裂斑块及血栓形成,而B组兔子未见斑块或血栓形成;所建立的破裂斑块在组织结构、细胞构成、生长特征和脂质沉积方面与人类斑块相似。结论液氮冻伤术能简便、快速、高效地建立AS破裂斑块及血栓模型,从而为研究人类AS破裂斑块及血栓形成的机理和药物干预治疗提供了一种新型动物模型。     

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties

Background and objectives

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.

Subjects and methods

Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.

Results

Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.

Conclusions

Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.     

Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease

Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value.     

瑞舒伐他汀治疗颈动脉粥样硬化斑块的临床研究

目的:研究瑞舒伐他汀对颈动脉粥样硬化斑块的治疗效果。方法:将在本院接受治疗的250例颈动脉粥样硬化斑块患者随机分成治疗组125例和对照组125例,治疗组服用瑞舒伐他汀10mg/晚,对照组行其他非瑞舒伐他汀药物治疗,进行为期6个月的观察对比。结果:治疗组治疗后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)水平显著下降,高密度脂蛋白(HDL)水平显著升高(P<0.05),颈动脉内膜-中层厚度(IMT)、斑块面积变小,与治疗前比较,差异有统计学意义(P<0.05);对照组治疗前后无显著性差异(P>0.05)。结论:瑞舒伐他汀对降低血脂、减缓不稳定型心绞痛早期动脉粥样硬化、稳定斑块和预防脑血管疾病起到非常重要的作用。